The objective of this project is to elucidate the epidemiology and ecology of Venezuelan hemorrhagic fever (VHF), an emerging viral zoonosis. VHF was first recognized in 1989; and the etiologic agent, Guanarito virus (family Arenaviridae), was isolated in 1991. During that period, about 104 cases of the disease with 26 deaths were reported to the Venezuelan Ministry of Health. At present, the disease appears to be confined to the central plains (llanos) region of the country. Preliminary field studies suggest that VHF is rodent-borne; humans probably acquire the virus by contact with excreta from infected wild rodents. The specific aims of the project are (1) to determine the incidence, prevalence and full geographic distribution of VHF, (2) to identify risk factors (environmental, behavioral, socioeconomic) for human infection with guanarito virus (GV) and to propose methods by which the transmission cycle can be interrupted, (3) to determine the hematologic and immune responses of humans to GV infection, (4) to study the pathogenesis of GV virus infection in its natural rodent hosts, (5) to examine the transmission dynamics of a representative arenavirus (Tamiami) in its natural rodent host under experimental laboratory conditions, and (6) to study the field ecology of the principal rodent reservoirs of GV in order to better understand the relationship between human and rodent infections. This project will consist of both field and laboratory studies; it will be a collaborative effort between scientists at Yale University, the Venezuelan Ministry of Health and the Centers for Disease Control.